Psoriasis is a chronic skin disease long recognized for its peculiar clinical symptoms characterized by circumscribed red patches covered with white scales, and often accompanied by varying degrees of discomfort. It has been determined that the disease is not contagious; however, its cause and mechanism have not yet been elucidated. See, Kruger, G. G., "Psoriasis: Current Concepts of its Etiology and Pathogenesis", The Year Book of Dermatology (1981). Due to the characteristic formation of skin lesions and eruptions, psoriasis gives its victims an unfavorable psychological outlook on life. Among people in Western countries, about 2% of the total population suffer from the disease.
Psoriasis is considered to be a pluricausal hereditary disease whose onset occurs due to the genetic makeup in the body, and which is stimulated by the action of various other factors, such as infection, drugs, food, climate and stress, any one of which can trigger the genetic cause. Since it is known that psoriasis has a close relationship with histocompatibility antigen (HLA) which exhibits polymorphism due to the variation of the HLA gene, it is clear that psoriasis is a hereditary disease.
The occurrence of psoriatic lesions and their remission are often alternately experienced over several years. There are two characteristic symptoms of psoriasis, namely, an inflammatory response common to that caused by other superficial skin diseases and a tendency toward growth of cuticle. Psoriasis is characterized by large, scaly patches of lesions on the skin, which may be reddened and inflamed. Many researchers have sought to elucidate the mechanism of the inflammatory response from the immunological viewpoint and the mechanism of the tendency to abnormal growth of cuticle from the cell physiological viewpoint. However, these mechanisms have not yet been successfully elucidated. See, Beutner, E. H., "Autoimmunity in Psoriasis" (CRC Press, Boca Raton, 1982).
Psoriasis is representative of those diseases accompanied by an inflammatory cornification of the skin, and the number of patients suffering from psoriasis is increasing. Various classifications have been proposed for psoriasis, but it is generally classified into psoriasis vulgaris, pustular psoriasis, psoriatic arthritis, guttate psoriasis, and the like. Of these, psoriasis vulgaris is the major type and accounts for 80 to 90% of all instances of the disease. When a person suffers from psoriasis, red maculae or red papules having clear borders occur on portions of the patient's body which are susceptible to external phlogogenic (inflammatory) stimuli, such as the head, elbows, knees and buttocks, and on areas where bacteria and fungi are likely to proliferate, such as pilose (hairy) regions of the body.
Various studies have heretofore been made on psoriasis, including conventional studies directed to the characterization of the morphological changes at the lesion site and more recent studies directed to the characterization of the biochemical and immunological changes at the lesion site. Nevertheless, the essential cause of psoriasis and the mechanism of occurrence of psoriatic lesions have not yet been elucidated. With respect to all types of psoriasis, various symptoms and phenomena are observed, such as hyperplasia and abnormal cornification of epidermal cells ascribed to the excess turnover of the cells by hypermetabolism; asthenia of inflammatory response in the epidermal papillary layer; vasodilation and serpiginous veins in the true skin; and polynuclear leukocyte migration and infiltration into the epidermal cell layers.
Representative of the therapeutic methods heretofore available to physicians seeking to treat psoriasis are the control of the hyperfunctional proliferation of epidermal cells; control of the inflammatory response; promotion of immunomodulation; and avoidance of infection by bacteria and fungi. For example, the following therapeutic methods have conventionally been utilized:
(1) External and internal use of adrenocortical hormone
The external or topical use of a steroid, has the immediate effect of reducing the symptoms of psoriasis, particularly the reduction of eruptions. However, administration of adrenocortical hormone over long periods of time that are necessary in such treatment causes tachyphylaxis, that is, an increased resistance and tolerance buildup, so that the dose must be increased, or stronger drugs must be used in order to obtain a desired therapeutic effect. Occasionally, the occurrence of a new lesion is observed at a site which has been treated with the drug. When adrenocortical hormone is applied to skin in the form of a coating, ointment, salve or paint, the hormone exerts its action not only on the lesion but also on the peripheral normal skin, so that atrophy and achromasia or loss of pigmentation of true skin, or steroid acne, is disadvantageously caused to occur on such areas of the skin.
Further, when the administration of the hormone is interrupted in order to avoid adverse effects of the drugs, withdrawal dermatitis is often caused so that the lesion is likely to expand and deteriorate. Such withdrawal dermatitis is caused particularly when the administration of an internal preparation is discontinued. Accordingly, when the lesion occurs on a relatively large area of skin, the disease cannot be completely cured by this method alone and, therefore, this mode of therapy must be combined with other therapies.
(2) Photochemotherapy
This method consists of administering psoralen in the form of an external or internal preparation and applying longwave ultraviolet rays to the diseased part. However, several types of psoriasis cannot be treated by this method. Moreover, it has the disadvantage in that when it is applied for a long period of time as in the case of heliotherapy, not only is a phenomenon similar to aging of the skin likely to occur, but also a peculiar lentigo or pigmented patch on the skin is likely to be formed.
(3) Phototherapy (UV Irradiation)
As in the case of heliotherapy, when ultraviolet irradiation is carried out for a long period of time, not only is accelerated aging of the skin likely to occur, but also carcinogenesis may be induced.
(4) External use of coal tar
Coal tar suppresses the growth of cells so that the lesion is diminished over a short period of time and a relatively long remission period may be achieved. However, occasionally, stimulant dermatitis and folliculitis (tar acne) may be caused.
(5) Administration of methotrexate
Methotrexate is an antagonist against follic acid, which is active in inhibiting the growth of cells. The use of methotrexate is effective for treating pustular psoriasis. However, the administration of methotrexate for a long period of time causes adverse effects, such as disturbance of liver function and suppression of myeloproliferation.
(6) Administration of retinoid
Retinoid is considered to have an immunomodulation effect, that is, it may control the abnormal cornification of epidermal cells and the hyperfunction of leukocyte migration. The internal administration of retinoid, such as etretinate, is particularly effective for treating pustular psoriasis and psoriatic erythroderma. However, retinoid often exhibits an adverse effect wherein the thickness of skin and visible mucous membrane become small. Further, abnormal levels of serum lipoprotein are occasionally observed. Moreover, retinoid is teratogenic and likely to accumulate and remain inside the body for a long period of time and, therefore, the application of retinoid to a person capable of childbearing is to be avoided. For this reason, retinoid is usually applied only to patients who are beyond childbearing age or who are suffering from intractable psoriasis.
As mentioned above, although the use of adrenocortical hormone exhibits an immediate effect of reducing the symptoms of psoriasis to some extent, tachyphylaxis is likely to occur, making the continued administration of the drug difficult. Further, owing to the tachyphylaxis, the dose must be disadvantageously increased. In such a case, when the administration is stopped in order to halt or avoid adverse effects, the symptoms may often become more severe due to the onset of withdrawal dermatitis. Accordingly, it is difficult to treat psoriasis effectively by the use of adrenocortical hormone alone. With respect to the other therapeutic methods, such as the photochemotherapy and therapy using an epidermal cell growth inhibitor such as coal tar, anthralin, methotrexate and retinoid, when these methods are used in combination with adrenocortical hormone, a therapeutic effect may be attained to some extent, but the psoriasis cannot be truly cured. See, Roenigk, H. H., Jr., and Maibach, H. I., "Psoriasis" (Marcel Dekker, New York, 1982).